Patten G S, Head R J, Abeywardena M Y, McMurchie E J
CSIRO Health Sciences and Nutrition, Kintore Avenue, P.O. Box 10041 Adelaide BC, 5000, Australia.
J Pharmacol Toxicol Methods. 2001 Jan-Feb;45(1):39-46. doi: 10.1016/s1056-8719(01)00116-2.
A modified apparatus is described that provides for the simultaneous bathing of the serosa of an intact piece of isolated guinea pig ileum while allowing infusion of the isolated lumen. The comparative compartmental potency of the opioid agonists morphine, casomorphins, and enkephalins to inhibit electrically driven contractions are described in this system. The rank-order potency for serosally applied opioid agonists was (IC(50) values, nM): [D-Ala(2),N-Me-Phe(4),Gly-ol(5)]-enkephalin (DAMGO) (15)>[D-Ala(2),D-Leu(5)]-enkephalin (DADLE) (35)> or =morphine (46)> or =[D-Ala(2)]-met-enkephalinamide (55)>[D-Ala(2)]-beta-casomorphin[1--4] amide (122)>beta-casomorphin[1--4] amide (940)>met- and leu-enkephalin (>6000). This contrasted to the rank-order potency for the luminally applied opioid agonists: DADLE (63)>DAMGO (135)>[D-Ala(2)]-met-enkephalinamide=morphine (4700)>[D-Ala(2)]-beta-casomorphin[1--4] amide (29000). beta-Casomorphin[1--4] amide, leu-enkephalin and met-enkephalin are mostly inactive when applied luminally. Furthermore, the opioid antagonists, casoxin 4 and [D-Ala(2)]-casoxin 4, when infused into the lumen, significantly overcame the inhibitory effect of morphine added to the serosal side. This model provides an assay and screening system to differentiate between the effects of chemical agents applied via the blood stream (serosa) or food side (lumen) on quiescent or electrically driven gut activity of the nervous plexi or receptor systems of the ileum.
本文描述了一种改良装置，该装置可在允许对分离的豚鼠回肠的孤立管腔进行灌注的同时，对完整的分离豚鼠回肠的浆膜进行同步灌注。本文还描述了阿片类激动剂吗啡、酪蛋白吗啡和脑啡肽在该系统中抑制电驱动收缩的相对区室效力。浆膜给药的阿片类激动剂的效力排序为（IC(50)值，纳摩尔）：[D-丙氨酸(2)，N-甲基苯丙氨酸(4)，甘氨酸醇(5)]-脑啡肽（DAMGO）（15）>[D-丙氨酸(2)，D-亮氨酸(5)]-脑啡肽（DADLE）（35）≥吗啡（46）≥[D-丙氨酸(2)]-甲硫氨酸脑啡肽酰胺（55）>[D-丙氨酸(2)]-β-酪蛋白吗啡[1-4]酰胺（122）>β-酪蛋白吗啡[1-4]酰胺（940）>甲硫氨酸和亮氨酸脑啡肽（>6000）。这与管腔给药的阿片类激动剂的效力排序形成对比：DADLE（63）>DAMGO（135）>[D-丙氨酸(2)]-甲硫氨酸脑啡肽酰胺 = 吗啡（4700）>[D-丙氨酸(2)]-β-酪蛋白吗啡[1-4]酰胺（29000）。β-酪蛋白吗啡[1-4]酰胺、亮氨酸脑啡肽和甲硫氨酸脑啡肽经管腔给药时大多无活性。此外，阿片类拮抗剂酪蛋白毒素4和[D-丙氨酸(2)]-酪蛋白毒素4经管腔灌注时，能显著克服添加到浆膜侧的吗啡的抑制作用。该模型提供了一种分析和筛选系统，可区分通过血流（浆膜）或食物侧（管腔）施加的化学试剂对回肠神经丛或受体系统处于静息或电驱动状态的肠道活动的影响。
